Morphine, an analgesic opiate, has high addiction liability. In general, there appears to be a high correlation between the analgesic action of an opiate, and its addiction liability. Using a sensitive and reliable microinjection technique (with fine- gauge cannula permanently implanted in certain subcortical sites) I have identified some sites which yield reliable hypo-or hyper-algesia following morphine microinjections. With this proven method, I propose to further study these sites with respect to: 1) dose-response relationship; 2) tolerance development; 3) interaction with naloxone; 4) effects of cholinergics and cholinolytics at these sites; 5) comparison with electrical stimulation using a modified cannula-electrode. The second part of this research will be concerned with ascertaining the addiction liability of those sites identified as having hypo- or hyper-algesic reactions to morphine. The operant conditioning technique of allowing animals to self-administer morphine will be used. Animals with and without a prior history of morphine addiction will be microinjected with the morphine antagonist, naloxone, to see if naloxone at these sites will affect operant responding for morphine self administration.